Suramin Discriminates Between the Calmodulin-Binding Sites of Neuronal and Inducible Nitric Oxide Synthase
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Authors
McNamara, Alyssa L.
Issue Date
2010
Type
Thesis
Language
en_US
Keywords
Alternative Title
Abstract
Nitric
oxide
synthase
(NOS)
continues
to
be
at
the
center
of
several
studies
as
it
is
a
formidable
target
for
drug
design.
Nitric
oxide
(∙NO),
the
product
of
the
NOS
reaction,
is
linked
to
a
number
of
pathological
conditions.
Suramin
is
a
polysulfonated
naphthylurea
that
has
specifically
been
shown
to
discriminate
among
calmodulin-‐binding
sites
on
proteins.
In
the
current
study,
suramin
was
shown
to
inhibit
both
neuronal
NOS
and
inducible
NOS,
however,
it
was
found
to
have
a
greater
effect
on
inducible
NOS.
Kinetic
analysis
showed
that
the
IC50
for
the
inducible
NOS,
in
the
absence
of
EDTA
is
approximately
41
μM,
but
in
the
presence
of
1
mM
EDTA,
is
2.6
μM.
IC50
of
the
neuronal
NOS
was
found
to
be
between
60
and
100
μM.
These
data
suggest
that
suramin
distinguishes
between
the
inducible
and
the
neuronal
NOS.
Western
analysis
further
suggests
that
suramin’s
distinction
of
the
NOS
forms
may
occur
through
its
interaction
at
the
calmodulin-‐binding
sites.
Docking
studies
indicate
that
suramin
binds
to
the
inducible
NOS
calmodulin-‐
binding
site
with
a
binding
energy
of
-‐14.32
kcal/mol.
These
results
point
to
a
new
NOS
target
site
for
drug
design.
Description
vi, 30 p.
Citation
Publisher
Kalamazoo College
License
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